Journal
CURRENT BIOLOGY
Volume 10, Issue 3, Pages 153-156Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/S0960-9822(00)00315-8
Keywords
-
Categories
Funding
- NHLBI NIH HHS [HL56949] Funding Source: Medline
- NIGMS NIH HHS [GM36624, GM54389] Funding Source: Medline
Ask authors/readers for more resources
Actin polymerization is essential for a variety of cellular processes including movement, cell division and shape change. The induction of actin polymerization requires the generation of free actin filament barbed ends, which results from the severing or uncapping of pre-existing actin filaments [1,2], or de novo nucleation, initiated by the Arp2/3 complex [3-7]. Although little is known about the signaling pathways that regulate actin assembly, small GTPases of the Rho family appear to be necessary [8-11]. In thrombin-stimulated platelets, the Rho family GTPase Rad induces actin polymerization by stimulating the uncapping of actin filament barbed ends [2]. The mechanism by which Pac regulates uncapping is unclear, however. We previously demonstrated that Pac interacts with a type I phosphatidylinositol-4-phosphate B-kinase (PIP 5-kinase) in a GTP-independent manner [12,13], Because PIP B-kinases synthesize phosphatidylinositol-4,5-bisphosphate (PI(4,5)P-2), a lipid that dissociates capping proteins from the barbed ends of actin filaments [14-16], they are good candidates for mediating the effects of Pac on actin assembly. Here, we have identified the Rac-associated PIP 5-kinase as the PIP B-kinase isoforms alpha and beta When added to permeabilized platelets, PIP B-kinase alpha induced actin filament uncapping and assembly. In contrast, a kinase-inactive PIP 5 kinase alpha mutant failed to induce actin assembly and blocked assembly stimulated by thrombin or Pac. Furthermore, thrombin- or Pac-induced actin polymerization was inhibited by a point mutation in the carboxyl terminus of Pac that disrupts PIP L-kinase binding, These results demonstrate that PIP B-kinase alpha is a critical mediator of thrombin- and Rac dependent actin assembly.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available